Larsen et al.

BMC Oral Health (2017) 17:103

DOI 10.1186/s12903-017-0393-2

RESEARCH ARTICLE Open Access

Oral symptoms and salivary findings in oral

lichen planus, oral lichenoid lesions and
stomatitis
Kristine Roen Larsen1*, Jeanne Duus Johansen2, Jesper Reibel1, Claus Zachariae3, Kasper Rosing4
and Anne Marie Lynge Pedersen1

Abstract
Background: To examine if patients with oral lichen planus, oral lichenoid lesions and generalised stomatitis and
concomitant contact allergy have more frequent and severe xerostomia, lower unstimulated and chewing-
stimulated saliva and citric-acid-stimulated parotid saliva flow rates, and higher salivary concentration of total
protein and sIgA than cases without contact allergy and healthy controls.
Methods: Forty-nine patients (42 women, aged 61.0 ± 10.3 years) and 29 healthy age- and gender-matched
subjects underwent a standardised questionnaire on general and oral health, assessment of xerostomia, clinical
examination, sialometry, mucosal biopsy and contact allergy testing.
Results: Nineteen patients had oral lichen planus, 19 patients had oral lichenoid lesions and 11 patients had
generalised stomatitis. 38.8% had contact allergy. Xerostomia was significantly more common and severe in
patients (46.9%) than in healthy controls, whereas the saliva flow rates did not differ. The patients had higher sIgA
levels in unstimulated and chewing-stimulated saliva than the healthy controls. The total protein concentration in
saliva was lower in the unstimulated saliva samples whereas it was higher in the chewing stimulated saliva samples
from patients when compared to healthy controls. The differences were not significant and they were irrespective
of the presence of contact allergy.
Conclusion: Xerostomia is prevalent in patients with oral lichen planus, lichenoid lesions and generalised stomatitis,
but not associated with salivary gland hypofunction, numbers of systemic diseases or medications, contact allergy,
age, or gender. Salivary sIgA levels were higher in patients than in healthy controls, but did not differ between
patient groups. The total salivary protein concentration was lower in unstimulated saliva samples and higher in
chewing-stimulated saliva samples in patients than in healthy controls, but did not differ between patient groups.
Our findings do not aid in the discrimination between OLP and OLL and these conditions with or without contact
allergic reactions.
Keywords: Oral lichen planus, Lichenoid lesions, Xerostomia, Salivary secretion, Total protein, sIgA

* Correspondence: krrl@sund.ku.dk
1
Section for Oral Pathology and Oral Medicine, Department of Odontology,
Faculty of Health and Medical Sciences, University of Copenhagen, 20 Noerre
Allé, DK-2200 Copenhagen N, Denmark
Full list of author information is available at the end of the article

© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Larsen et al. BMC Oral Health (2017) 17:103
Background
Oral lichen planus (OLP) is one of the most common
oral mucosal lesions affecting 0.5% to 2% of the adult
population [1–4]. OLP mainly affects middle-aged and
elderly, and is more prevalent in women than in men [5–7].
OLP may present as reticular, erythematous, ulcerative,
plaque-like, bullous and papular lesions affecting predomin-
antly the buccal mucosa, gingiva and tongue [3, 5, 6, 8].
The etiology is unknown, but the pathogenesis is
believed to involve a T-cell-mediated response. However,
the mechanisms triggering the T-cells to enter the oral
epithelium and to accumulate in the superficial lamina
propria as well the triggering mechanisms behind basal
keratinocyte apoptosis are not fully understood, and may
involve both antigen-specific and non-specific mecha-
nisms [9]. The diagnosis of OLP is based on fulfillment
of clinical and histopathological criteria [10, 11]. Lesions
that are clinically and histopathologically similar to OLP
may occur as a reaction to certain systemic medications
[12] or dental materials [13–15] and are referred to as
oral lichenoid lesions (OLL). Also oral hygiene substances,
like flavorings, may trigger lichenoid contact sensitivity
reactions [16, 17]. At present it may be difficult to distin-
guish between OLP and OLL. Patients with the erythema-
tous and ulcerative type of OLP often suffer from severe
oral mucosal soreness, including burning and itching sen-
sations, particularly in relation to the intake of spicy and
acidic food, which may have a negative impact on oral
functions as well as the patients’ quality of life and well-
being [18]. In addition, we have previously shown that
45% of patients with erythematous and ulcerative OLP
also suffer from xerostomia (the subjective feeling of dry
mouth) and a sensation of very viscous saliva [18]. These
findings have been substantiated by other studies, demon-
strating an association between OLP and OLL and xeros-
tomia [19, 20]. OLP and OLL may occur in conditions
that are associated with xerostomia and salivary gland
hypofunction, including Sjögren’s syndrome, hepatitis C
infection, type 1 diabetes, and graft-versus-host disease
[21–26]. Patients with these conditions often also display
immune-mediated sialoadenitis which may affect the func-
tion of the salivary glands. However, it is still debatable
whether the complaints of dry mouth and other sicca
symptoms should be ascribed the OLP/OLL alone or
whether they reflect a pathogenic association to systemic
autoimmune diseases in which xerostomia and salivary
gland dysfunction are common clinical manifestations.
We have previously shown that only 15% of the 45% OLP
patients who complained about xerostomia, actually had
hyposalivation (i.e., an unstimulated whole saliva flow rate
below ≤0.10 ml/min), and this could be related to a daily
intake of cardiovascular medications including antihyper-
tensives known to cause xerostomia and/or hyposalivation
[18, 27, 28]. A study on salivary gland function and
Page 2 of 9
morphology showed that 87% of 39 patients with OLP
had a low or very low unstimulated whole saliva flow rate,
whereas the chewing-stimulated whole saliva flow rate,
the buffering capacity and the salivary pH level were nor-
mal. A labial salivary gland biopsy was performed in 15
patients, revealing lymphocytic infiltration (in 80%), acinar
atrophy (in 93%), fibrosis, fatty degeneration, or ductal
changes. However, although they displayed comparable
signs of Sjögren’s syndrome, none fulfilled the classifica-
tion criteria [29]. Another study on 100 patients with OLP
found no associations between OLP and low unstimulated
and citric acid stimulated whole saliva flow rates [30].
Xerostomia denotes the subjective feeling of oral
dryness, and it is often caused by salivary gland hypo-
function, but may occur in the presence of an apparently
normal salivary secretion, indicating that not only quantity
but also quality of saliva is of importance to the feeling of
oral comfort [31, 32]. Accordingly, changes in saliva com-
position may affect mucosal adhesiveness and lubrication
[33]. Moreover, salivary secretion can be reduced as much
as 50% of a person’s normal whole saliva flow rate, before
the sensation of oral dryness occurs [34]. Regarding
changes in saliva composition, it has recently been
reported that the total protein concentration was higher
in patients with OLP than in healthy control subjects [35].
However, Gandara and co-workers found no differences
between patients with OLP and healthy controls in terms
of saliva flow rates, salivary proteins and electrolytes [36].
Moreover, it has been shown that patients with OLP and
OLL have higher levels of salivary immunoglobulins IgA
and IgG than healthy control subjects [35, 37, 38].
Secretory immunoglobin A (sIgA) and immunoglobulin G
(IgG) are the two major classes of antibodies in human
saliva comprising, 90–98% and 1–10%, respectively [39]. It
has been suggested that both serum and salivary immuno-
globulins, and particularly sIgA and IgG, play an import-
ant role in the pathogenesis of OLP, and it has also been
hypothesised that the levels of sIgA and IgG could be use-
ful in discriminating the OLP from OLL [38].
The aim of this cross-sectional study was to examine
whether xerostomia, the degree of xerostomia, the
unstimulated and chewing-stimulated whole saliva and
citric-acid-stimulated parotid saliva flow rates, and the
salivary concentration of total protein and sIgA could be
used as diagnostic tools in discriminating between
patients with OLP, OLL and generalised stomatitis with
and without contact allergy.
We hypothesised that patients with OLP, OLL and gen-
eralised stomatitis and concomitant contact allergies have
a higher frequency of xerostomia, more severe xerostomia,
lower unstimulated and chewing-stimulated whole saliva
and citric-acid-stimulated parotid saliva flow rates, and
higher salivary concentration of total protein and sIgA
than patients with OLP, OLL and stomatitis but without
Larsen et al. BMC Oral Health (2017) 17:103
contact allergies; and healthy age- and gender-matched
control subjects.
Methods
The study was approved by the Regional Ethics Commit-
tee, Copenhagen, Denmark (no. H-3-2013-033, March
26th 2013) and conducted according to the Declaration of
Helsinki. The participants were both informed by letter
and orally and all gave written consent prior to inclusion.
Study participants
One hundred and thirty-four consecutive patients referred
to the Clinic for Oral Medicine, Department of Odontol-
ogy, Faculty of Health and Medical Sciences, University of
Copenhagen, due to symptoms and signs of oral mucosal
diseases were screened for inclusion in the study. Fifty-two
Caucasian patients were eligible for inclusion of whom 49
(94.2%) completed the study. The remaining patients were
excluded due to other diagnoses than OLP, OLL and sto-
matitis, and in cases where intake of medication was sus-
pected as the eliciting cause of their mucosal lesions.
Twenty-nine healthy age- and gender-matched subjects
were included via the Danish website for study subjects
(www.forsoegsperson.dk). The exclusion criteria for this
group were past or current history of systemic and oral dis-
eases as well as intake of medication. As it proved difficult
to recruit healthy non-medicated control subjects at the
age above 65 years, 4 persons taking antihypertensives (but
otherwise healthy) were matched to the patients with
regard to gender, age and type of antihypertensive agent.
An oral smear was taken from all study participants
prior to inclusion in order to exclude oral candidiasis as
it may mimic other mucosal lesions, e.g. erythematous
OLP. A superimposed fungal infection may also mas-
querade the pattern of OLP lesions and be the cause of
oral symptoms. The smear was stained with Periodic
Acid Schiff and evaluated cytologically for presence of
yeast hyphae and spores. Eleven patients, but none of
the healthy subjects, had an oral candidiasis. They were
treated with nystatin for 4 weeks, prior to inclusion. The
treatment had no impact on their oral symptoms, but
according to a repeated smear, the hyphae and spores
were eliminated.
All patients had oral symptoms including stinging and
burning sensations, and were diagnosed with OLP, OLL
or generalised stomatitis. The patients with OLP and
OLL were clinically characterised by various combina-
tions of reticular, erythematous, ulcerative and plaque-
like mucosal changes and the diagnosis was confirmed
by a biopsy and histopathological examination according
to van der Meij and van der Waal [11]. However, this
method to discriminate between OLP and OLL still
needs to be validated in larger scale studies. The patients
diagnosed with stomatitis were characterised by having a
Page 3 of 9
more diffuse, widespread oral mucosal erythema. The
patients with OLP and OLL were pooled in one group
as a strict distinction between the two entities was diffi-
cult to make.
All participants underwent a mucosal biopsy at the
Department of Odontology, University of Copenhagen,
and were referred for patch testing for contact allergy at
the Department of Dermatology and Allergy, Gentofte
University Hospital. Patch testing to the European base-
line series, a toothpaste series and a dental material
series were done according to the European Society of
Contact Dermatitis (ESCD) guidelines [40]. Moreover,
all participants had a check of the serum levels of
thyroid stimulating hormone (TSH). They also under-
went an interview including standardised questions
regarding present and past systemic diseases, including
allergies, daily intake of medication, habits regarding
alcohol consumption, tobacco smoking and oral hygiene.
Data on smoking habits was used to categorize partici-
pants as never smokers, former smokers and current
smokers. Data on alcohol consumption was used to pool
the participants in groups of never consuming alcohol,
occasionally or daily consumption of alcohol.
Assessment of xerostomia
Apart from being questioned about symptoms of the oral
mucosa like stinging, burning and roughness, the partici-
pants were also asked whether they had taste disturbances
and the character of their disturbances in taste perception.
Moreover, the participants were asked whether they had
symptoms of dry mouth, and if present they were also
asked to score the severity of xerostomia using a catego-
rized questionnaire based on Beck’s inventory scale on
how questionnaires should be designed in order to obtain
valid responses [41] including four degrees of severity
(scores 0–3) [42]. The assessment also included potential
affection of oropharyngeal functions and diurnal variation
in the sensation of oral dryness (Table 1).
Measurements of whole saliva and parotid saliva flow rates
One examiner (KRL) conducted the collection of
the whole saliva and the parotid saliva. In brief, the par-
ticipants were asked to refrain from drinking, eating,
chewing chewing-gum/pastilles, tooth brushing and
smoking for one hour prior to the salivary measurement.
The whole saliva samples were collected using the drain-
ing method [43]. Unstimulated and paraffin-chewing-
stimulated whole saliva flow rates (UWS and SWS,
respectively) were sampled over a 15-min and a 5 min-
period, respectively. The citric acid stimulated parotid
saliva (SPS) was sampled over a 5-min period [43]. To
minimize the influence of the circadian cycle on the
composition and flow rate of saliva, all procedures were
performed in the same order between 9.00 am and
Larsen et al. BMC Oral Health (2017) 17:103 Page 4 of 9

Table 1 Questionnaire regarding xerostomia and scoring of the of IgA (μg/min) was determined by each concentration
severity of xerostomia by patients and healthy controls [41] was multiplied with the respective salivary flow rate (ml/
Category Patients Healthy min).
n = 49 controls n = 29
No feeling of dry mouth (score 0) 53. 1% 79.3% Statistics
Slight feeling of dry mouth (score 1) 26.5% 20.7% The statistical analyses were performed using SPSS
Severe feeling of dry mouth (score 2) 8.2% 0% Version 22 (IBM). Fisher’s test was used for analysis of
Annoying feeling of dry mouth 12.2% 0%
distributions between the patient group, including those
making speech difficult (score 3) with or without a concomitant contact allergy, and the
Difficulty swallowing due to xerostomia 12.2% 0% healthy control group. As the saliva flow rates (UWS,
SWS and SPS) were not normally distributed in the pa-
Difficulty chewing due to xerostomia 10.2% 0%
tient group, the Mann–Whitney U test was used. A t-test
Difficulty in eating dry food substances 32.7% 0%
due to xerostomia
was used after fulfilling the Shapiro-Wilk’s and Levene’s
tests, when comparing the data from the patients with
Taste perception different from normal 28.6% 0%
OLL with and without a concomitant contact allergy. The
-increased taste perception 4.1% 0% Mann–Whitney U test was used for comparisons in saliv-
-decreased taste perception 18.4% 0% ary total protein and sIgA between the patients and the
-no taste perception 4.1% 0% healthy control subjects, and between patients with OLL
-altered taste perception (dysgeusia) 14.3% 0% with and without a concomitant contact allergy. Associa-
Nocturnal xerostomia 24.5% 13.8% a
tions between variables were analysed by the Spearman
rank order correlation test. Statistical significance was
Morning xerostomia 36.7% 24.1%a
defined as p < 0.05.
Daytime xerostomia 22.4% 3.4%
Evening xerostomia 10.2% 0% Results
Xerostomia at all times of the day 10.2% 0% About 85% of the participants were women, and the
Waking up due to xerostomia 34.7% 17.2%a average age was 61 years (median 65 years, range 32–77
Duration of xerostomia, years 2,88 2
years). Three patients used tobacco on a daily basis and
on average they had smoked 21.5 smoking pack years.
Number of participants reporting symptoms are given in percentage.
a
Reported to be caused by periodic snoring, in periods without snoring they Four healthy controls used tobacco daily and they had
did not have xerostomia on average smoked 17.3 smoking pack years. Nineteen
patients and 14 healthy controls had ceased smoking
11.00 am every time. The saliva samples were immediately more than one year prior to the inclusion in the project.
weighed so that the flow rates could be established and Seven patients and eleven healthy controls reported a
then portioned in 1.5 ml Eppendorf tubes, centrifuged at daily consumption of alcohol. One male patient reported
10.000 g for 20 min at 4o C, portioned and frozen at -80o an alcohol consumption that exceeded the 21 units of alco-
C until further analysis. UWS values of ≤0.10 ml/min and hol per week limit as recommended by the Danish Health
SWS values of ≤0.70 ml/min were designated hyposaliva- Authority. Forty-six (85.7%) patients reported having one
tion [42]. Patients with UWS flow rates below 0.20 ml/ or more medical condition/disease (median 2, range 1–12).
min were designated as low secretors [44]. The most common ones included recurrent herpes labialis
(herpes simplex virus, n = 20), hypertension (n = 11), osteo-
Clinical oral examination arthritis (n = 12), contact dermatitis (n = 9) and asthma (n
One examiner (KRL) conducted the oral clinical examin- = 7). Furthermore, 6 patients had pollen allergy, 7 had con-
ation, calibrated against an experienced clinical examiner tact allergy to nickel and 5 had allergy to fragrance ingredi-
(AMLP). The localisation, size and colour of the oral ents. These were all confirmed prior to the inclusion in the
lesions were registered and clinical photos were taken. project by testing. General information on the participants
Also the clinical signs of mucosal dryness were registered. can be seen in Table 2.
Thirty-two (65.3%) patients reported daily intake of pre-
Analyses of salivary total protein and sIgA scribed medication (median 2, range 1–10), most com-
The total protein concentration (μg/ml) in unstimulated monly antihypertensives. Sixteen (32.6%) patients had a
and chewing-stimulated whole saliva was determined daily intake of more than two different types of medica-
using a colorimetric assay [45]. An indirect enzyme tion (i.e., polypharmacy), 7 patients took two types of
immunoassay kit was used to determine sIgA in medication daily and 9 patients one type of medication
the whole saliva samples according to the protocol sup- daily. Three female patients (6%) had hypothyroidism and
plied by Salimetrics® (Salimetrics, PA, USA). The out-put one female patient had hyperthyroidism. Blood samples
Larsen et al. BMC Oral Health (2017) 17:103 Page 5 of 9

Table 2 Clinical characteristics of the patients and healthy aroma substances in oral hygiene products differed sig-
controls nificantly between the patients and the healthy control
Patients Healthy controls subjects (p = 0.02), primarily in patients with OLP and
(n = 49) (n = 29) OLL (p = 0.01). Spearmint was the most common aller-
Female:male ratio 42:7 25:4 gen in the patient group, whereas it was cassia oil in the
Age, years 61.0 ± 10.3 58.2 ± 12.1 healthy controls. The substances that the participants
(range 31–77) (range 23–73) primarily displayed positive patch test reaction to are
Smoking, percentage (smoking pack year) listed in Table 3.
-non 55.1% (0) 37.9% (0) Table 1 shows the distribution of xerostomia in terms
-former 38.8% (21.2) 48.3% (12.8) of severity of xerostomia and any diurnal variations in
the patient group with OLP/OLL and stomatitis and the
-current 6.1% (21.5) 13.8% (17.3)
healthy control group. Expectedly, the patients had
Alcohol consumption, percentage
significantly more complaints of xerostomia and more
-never 61.2% 17.2% severe xerostomia than the healthy control subjects (p <
-occasionally 24.5% 44.8% 0.001). However, there were no differences in the
-daily 14.3% 37.9% frequency of xerostomia between patients with OLP,
Chronic medical conditions (no. given in%) OLL and stomatitis, and patients with and without a
concomitant contact allergy (p = 0.30). There were no
-herpes labialis 40.8% 41.4%
associations between the presence and severity of xeros-
-hypertension 24.5% 6.9%
tomia and age, gender, number of medical conditions/
-osteoarthritis 24.5% 6.9% diseases, including allergies, or the number of medica-
-hypercholesterolaemia 10.2% 6.9% tions taken on a daily basis. More female patients than
-allergic rhinitis 12.2% 0% male patients reported xerostomia, but the majority of
-asthma 14.3% 3.4% the study population also comprised women. 28.6% of
the patients reported that they experienced their taste
-contact allergy 38.8% 34.5%
perception to be different from normal, primarily as a
Data are given in mean and SD
decreased or an altered taste perception.
The salivary flow rates are listed in Table 4. No differ-
analyzed for levels of thyroid stimulating hormone (TSH) ences could be found between the patient group and the
revealed that all patients but two had TSH levels within the healthy control group or between the patients with OLP,
normal range. In one patient with known hypothyroidism,
the level of TSH was elevated, and her medical treatment
Table 3 Substances that the participants primarily displayed
was consequently regulated. In another patient with known positive patch test reaction to
hyperthyroidism, the level of TSH was decreased, and her
Substances with positive patch test reactions Patients Healthy controls
medical treatment was adjusted accordingly. In none of (n = 49) (n = 29)
these two patients, the adjustments in their treatment lead Perfume mix 7 4
to changes in their oral condition. Three healthy control
Balsam of Peru 5 1
subjects showed elevated levels of TSH and were referred to
Colophony 4 0
additional medical examinations of possible hypothyroidism.
There were no associations between age, gender and the Spearmint 4 0
number of medical conditions/diseases and the number of Cassai oil 3 1
medication taken on daily basis. Carvone 2 0
The diagnosis of OLP was established in 19 patients Cinnemaldehyd 1 0
and additionally 19 patients were diagnosed with OLL.
Nickel 2 4
Fifteen patients had the erosive form of OLP at the time
Mercury 2 0
of the examination. As an exact distinction between
OLP and OLL was difficult to make, we pooled the pa- 2-hydroxyethyl-methacrylate 2 0
tients in one group comprising both OLP and OLL. Methylmethacrylate (MMA) 1 0
None of the patients were diagnosed with hepatitis C, Ethylen glycol dimethacrylate (EDGMA) 1 0
Sjögren’s syndrome or any other autoimmune disease. Palladium 1 1
The diagnosis of stomatitis was made in 11 patients
Cobalt 1 1
(22.4%). Nineteen patients (38.8%) and 10 (34.5%)
Some participants displayed more than one positive patch test reaction which
healthy control subjects were diagnosed with contact explains why the total number adds up to more than the number of patients
allergy, primarily to fragrance mix. Contact allergy to and healthy controls [56]
Larsen et al. BMC Oral Health (2017) 17:103
Table 4 Unstimulated (UWS), paraffin-chewing-stimulated (SWS)
and citric-acid-stimulated parotid (SPS) saliva flow rates (ml/min),
total salivary protein concentration (μg/min) and salivary sIgA levels
(μg/min) in unstimulated and chewing-stimulated whole saliva
Patients Healthy controls p-value
(n = 49) (n = 29)
UWS (ml/min) 0.33 ± 0.21 0.39 ± 0.25 0.33
SWS (ml/min) 1.69 ± 1.03 1.75 ± 0.72 0.25
SPS (ml/min) 0.15 ± 0.16 0.15 ± 0.12 0.56
Total protein concentration
(μg/min)
-UWS 1047.9 ± 633.0 1131.0 ± 640.1 0.86
-SWS 4317.6 ± 2414.6 4090.0 ± 1689.1 0.58
Levels of sIgA (μg/min)
-UWS 48.6 ± 29.5 47.8 ± 21.79 0.82
-SWS 96.1 ± 51.7 82.4 ± 38.1 0.19
All data are given in mean and SD
OLL and generalised stomatitis with and without a
concomitant contact allergy regarding the UWS, SWS
and SPS flow rates. However, the UWS flow rates tended
to be lower in patients with OLP/OLL and concomitant
contact allergy than in those without contact allergy
(p = 0.05). One patient had severely reduced UWS, SWS
and SPS with UWS flow rates below 0.10 ml/min and
SWS flow rates ≤0.70 ml/min. Three other patients had
UWS hyposalivation, whereas 10 patients were charac-
terised as low secretors. Moreover, two patients had SWS
flow rates ≤0.70 ml/min, but normal UWS flow rates. One
healthy control subject had UWS hyposalivation and 8
were low secretors, but SWS flow rates were in the
normal range. There were no associations between the sal-
ivary flow rates (UWS, SWS and SPS) and age, gender,
number of medical conditions/diseases, the number of
medications taken on a daily basis or the prevalence and
severity of xerostomia. The patients with UWS hyposali-
vation had a salivary gland biopsy taken from the minor
glands in the mucosa of the lower lip under the suspicion
of Sjögren’s syndrome. None of them had focal lympho-
cytic infiltration in their glandular tissue or serum auto-
antibodies, excluding Sjögren’s syndrome. The SPS flow
rates did not differ between the patients and the healthy
controls or between the patients with and without a con-
comitant contact allergy.
The total protein concentration in terms of output
(μg/min) in unstimulated and chewing-stimulated
whole saliva from patients and healthy control sub-
jects are listed in Table 4. The patients had higher
total protein concentrations in unstimulated whole
saliva while it was lower in chewing-stimulated whole
saliva but the differences were not significant (p =
0.58 and p = 0.86 respectively), whereas there were no
differences in the total salivary protein concentrations
Page 6 of 9
when comparing patients with OLL with and without a
concomitant contact allergy.
The levels of sIgA in terms of output (μg/min) in both
unstimulated and chewing-stimulated whole saliva from
patients and healthy control subjects are shown in
Table 4. The levels of sIgA were higher in both unstimu-
lated and chewing-stimulated whole saliva in patients
than in healthy control subjects but the difference was
not significant (p = 0.82 and p = 0.19 respectively). No
difference could be found in the salivary sIgA levels
when comparing patients with OLP/OLL with and with-
out a concomitant contact allergy.
Discussion
The aim of this cross-sectional study was to determine if
xerostomia, degree of xerostomia, UWS, SWS and SPS
flow rates and levels of salivary protein concentration
and sIgA could be used in discriminating between
patients with OLP/OLL and generalised stomatitis with
or without concomitant allergy and healthy control
subjects.
The majority of patients included in this study were fe-
males, which reflects the fact that more women than
men are referred to medical clinics and that OLP/OLL
are more prevalent in women. However, it also explains
the high prevalence xerostomia and other symptoms, the
high number of medical diseases/medical conditions and
number of medications taken on a daily basis in our
study. Furthermore, the age of onset of OLP also indi-
cate that gender hormones may be involved in the
pathogenesis via immunological and endocrinological
changes affecting the oral mucosa and the immuno-
logical response and making the mucosa more suscep-
tible to oral diseases like OLP and allergic reactions.
The diagnosis of OLP and OLL was established in 38
patients (77.6%) according to the recommendations of van
der Meij and van der Waal [11]. Although the latter seeks
to differentiate between OLP and OLL based on clinico-
pathological criteria, the value of distinction between
them is still controversial. The remaining 11 patients were
diagnosed with generalised stomatitis. These patients dis-
played more diffuse reactions varying from barely visible
erythema to bright red erythema anywhere in the oral mu-
cosa. Erosions and hyperkeratosis were also seen as previ-
ously described [46]. In our study, we did not find a clear
distinction between OLP and OLL with respect to the
symptoms and the clinicopathological features.
It is well known that OLL may occur as adverse reac-
tions to systemic drugs including angiotensin-converting
enzyme (ACE) inhibitors and beta-blockers [12, 47]. In
this study, we eliminated cases in which there was a
clear temporal association between the intake of medica-
tion and the onset of oral symptoms and signs of OLL.
In these cases we found that discontinuation of the
Larsen et al. BMC Oral Health (2017) 17:103
medication also resulted in a gradual disappearance of
the lichenoid reactions.
As expected, xerostomia was reported significantly more
often by the patients (46.9%) than healthy control subjects
(20.7%). We did not find any differences between the pa-
tients with OLP/OLL and generalised stomatitis with and
without contact allergies in terms of prevalence and sever-
ity of xerostomia. It is well-known that certain systemic
diseases and the intake of certain medications as well as
the number of diseases and medications are associated
with xerostomia [28, 48–51]. In our study, 65.3% of the
patients reported daily intake of medication and 32.6%
had an intake of more than 2 different agents on a daily
basis, which is reflecting the medication intake in the
background population. Several of the medications taken
by the participants in our study are known to be “xero-
genic” [27, 28]. This might explain the difference in the re-
ports of xerostomia between the patients and the healthy
controls. However, we did not find significant associations
between the number of medical conditions/diseases, the
number of medications and the presence and severity of
xerostomia, which may reflect the fact that there were
relatively few observations in each category of diseases
and medications. However, there was tendency towards an
association between the intake of antihypertensives and
xerostomia. On the other hand, the sensation of dry
mouth could also be solely related to OLP or OLL as pre-
viously described [18–20]. It is also well-known that
women report xerostomia more frequently than men [48]
and, as mentioned earlier, the majority of patients in-
cluded in this study were women. In the healthy control
group, 20.7% reported a “slight sensation of dry mouth”,
which was related to awakening and “snoring”. Xerosto-
mia is often associated with salivary gland hypofunction,
but in our study we did not find any associations between
xerostomia, the severity of xerostomia and the salivary
flow rates. Thus, it is likely that the inflammatory changes
in the oral mucosa due to OLP, OLL and generalised sto-
matitis lead the sensory disturbances, including sensation
of oral dryness [52].
We found no significant differences in UWS, SWS
and SPS flow rates between the patients with and
without concomitant allergies and the healthy control
subjects, although there was a tendency towards
lower UWS flow rates in patients with OLP/OLL and
a concomitant contact allergy. Our findings are in
concordance with several other studies showing that
the salivary flow rates in patients diagnosed with OLP
do not differ from the salivary flow rates in healthy
control subjects [18, 20, 36, 37].
We found no associations between age, gender and
the number of diseases and the number of medication
taken on daily basis, which can be ascribed to the very
narrow variation in age (the median age was 65 years).
Page 7 of 9
We found higher total protein concentrations in
chewing-stimulated saliva samples from patients with
OLP/OLL and generalised stomatitis compared to those
from healthy control subjects whereas the opposite could
be seen in the unstimulated saliva samples. These differ-
ences were not significant. Changes in saliva composition
can contribute to explain sensation of dry mouth. Our
findings are in concordance with Gandara et al. [36] and
Artico et al. [20], who found no differences in total protein
concentration between patients with OLP and healthy
controls. We found no difference either in the total saliv-
ary protein concentration between patients with OLP/
OLL with and without a concomitant contact allergy.
In our study, the levels of salivary sIgA were higher in
both unstimulated and chewing-stimulated whole saliva
samples from patients than in those from the healthy
control subjects, but the difference was not significant.
Previous findings on the levels of salivary sIgA concen-
trations are contradictory [35–38]. SIgA is an important
part of the immune defense of mucosal surfaces. Salivary
IgA can be used to evaluate the immune state and very
high levels can indicate underlying pathology [37, 53, 54].
We found no difference in the salivary sIgA levels when
comparing patients with OLP/OLL with and without a
concomitant contact allergy.
A recent study showed that thyroid disease was
present in 33 of 215 (15.3%) of patients with OLP com-
pared to 12 of 215 (5.2%) in a control group [55]. How-
ever, in our study only 4 patients (6.1%) had a thyroid
disease and the serum levels of TSH revealed that three
of the healthy control might have hypothyroidism.
It is likely that the higher prevalence and more severe
xerostomia, the higher salivary concentrations of total
protein and levels of sIgA that we find may be ascribed to
a higher degree of anxiety, depression and sleep distur-
bances in the patient group. These speculations are
supported by a recent study of Lopez-Jornet et al. [35]
showing that patients OLP presented worse psycho-
logical profiles and sleep disturbances, and also higher
values for sIgA, cortisol, and total proteins than con-
trol subjects.
Conclusion
Our findings indicate that OLP, OLL and generalised stoma-
titis are associated with xerostomia. However, xerostomia
was not associated with reduction in the salivary flow rates,
the number of diseases or number of medications taken on
a daily basis, age or gender. There were no differences in
UWS, SWS and SPS flow rates between the patients with
OLP/OLL and generalised stomatitis and healthy control
subjects. On the other hand, the salivary concentrations of
total protein and the levels of sIgA were higher in the
patient group than in the healthy control group even though
the difference was not significant. However, these findings
Larsen et al. BMC Oral Health (2017) 17:103
do not aid in the discrimination between OLP and OLL and
these conditions with or without contact allergic reactions.
Abbreviations
ESCD: European Society of Contact Dermatitis; IgG: Immunoglobulin G; OLL: Oral
lichenoid lesions; OLP: Oral lichen planus; sIgA: Secretory immunoglobulin A;
SPS: Citric acid stimulated parotid saliva; SWS: Chewing stimulated whole saliva;
TSH: Thyroid stimulating hormone; UWS: Unstimulated whole saliva
Acknowledgements
Thanks to laboratory technicians Louise Rosgaard Duus and Joan Lykkeaa for
assistance with the laboratory work.
Funding
Faculty of Medical and Health Science, University of Copenhagen, the Danish
Dental Association Research Foundation and Toyota Fonden, Denmark.
Availability of data and materials
The clinical data and personal details will not be made available in order to
protect the participants’ identity.
Authors’ contributions
Substantial contributions to the design of the study: AMLP, JDJ and JR.
Substantial contributions to the acquisition of data: KRL, AMLP, JDJ, JR and
CZ. Substantial contributions to the analysis of data: AMLP and KR.
Substantial contributions to the interpretation of data: KRL and AMLP.
Authoring the first draft: KRL. Critically revising the manuscript: All authors.
All authors read and approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Consent for publication
Not applicable.
Ethics approval and consent to participate
The study was approved by the Regional Ethics Committee, Copenhagen,
Denmark (no. H-3-2013-033, March 26th 2013) and conducted according to
the Declaration of Helsinki. The participants were both informed by letter
and orally and all gave written consent prior to inclusion.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
Author details
1
Section for Oral Pathology and Oral Medicine, Department of Odontology,
Faculty of Health and Medical Sciences, University of Copenhagen, 20 Noerre
Allé, DK-2200 Copenhagen N, Denmark. 2National Allergy Research Centre,
Department of Dermatology and Allergy, Gentofte University Hospital, 28
Kildegaardsvej, DK-2900 Hellerup, Denmark. 3Department of Dermatology
and Allergy, Gentofte University Hospital, 28 Kildegaardsvej, DK-2900
Hellerup, Denmark. 4Section for Community Dentistry, Department of
Odontology, Faculty of Health and Medical Sciences, University of
Copenhagen, 20 Noerre Allé, DK-2200 Copenhagen N, Denmark.
Received: 10 February 2017 Accepted: 16 June 2017
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